sorafenib + topotecan for platinum-resistant recurrent ovarian cancer

Conditions: Ovarian Cancer

Summary: this multi-institutional phase i/ii clinical trial will test the tolerability and efficacy of the combination sorafenib and topotecan in patients with recurrent ovarian cancer, which is platinum-resistant (recurrence within 6 months from completing platinum based therapy) or refractory (progressive disease during platinum based therapy).

outline: this is a multi-center study. * topotecan: 4mg/m2 weekly, 3 weeks on and one week off. * sorafenib: assigned cohort dose for phase i (up to 12 patients) maximum tolerated dose for phase ii (21 total patients) cycles will consist of 4 weeks (28 days) with disease evaluations every 8 weeks. non-pd and acceptable toxicity: patients will continue protocol therapy pd or unacceptable toxicity: patients will discontinue protocol therapy ecog performance status 0-1 life expectancy: three (3) months hematopoietic: * white blood cell count (wbc) \> 3 k/mm3 * hemoglobin (hgb) \> 9 g/dl * platelets \> 100 k/mm3 * absolute neutrophil count (anc) \> 1.5 k/mm3 * inr \< 1.5 or a ptt within normal limits. note: patients receiving anti-coagulation treatment with an agent such as warfarin or heparin may be allowed to participate. * no evidence or history of bleeding diathesis or coagulopathy. hepatic: * bilirubin \< 1.5 x uln * aspartate aminotransferase (ast, sgot) \< 2.5 x uln * alanine aminotransferase (alt, sgpt) \< 2.5 x uln * alkaline phosphate \< 2.5 x uln renal: * creatinine \< 1.5 x uln cardiovascular: * no history of myocardial infarction or angina pectoris or angina equivalent within 6 months prior to registration for protocol therapy (the patient may not be on anti-anginal or anti-arrhythmic medications), or have uncontrolled hypertension or congestive heart failure \> class ii nyha pulmonary: * no thrombolic or embolic events such as a cerebrovascular accident, including transient ischemic attacks within the past 6 months. * no pulmonary hemorrhage/bleeding event \> ctcae grade 2 within 28 days prior to registration for protocol therapy. * no non-pulmonary hemorrhage/bleeding event \> ctcae grade 3 within 28 days prior to registration for protocol therapy.

Eligibility criteria:
inclusion criteria: * have histologically-confirmed epithelial ovarian cancer, primary peritoneal carcinomatosis or fallopian tube cancer. enrollment of patients with clear cell histology is encouraged. * have measurable disease according to recist or detectable disease by 1) ca-125 at least twice the uln within 14 days prior to registration for protocol therapy; 2) ascites and/or pleural effusion attributed to tumor; 3) solid and/or cystic abnormalities on radiographic imaging that do not meet recist definitions for target lesions. * have failed at least one prior platinum based chemotherapeutic regimen. * no more than 3 prior treatment regimens for epithelial ovarian cancer. * prior radiation therapy is allowed to \< 25% of the bone marrow. * be at least 4 weeks since last anti-cancer treatment, radiation or surgery at the time of registration for protocol therapy. * no active cancer in addition to the epithelial ovarian cancer within the last 5 years, with the exception of: superficial skin cancer (basal cell or squamous cell skin carcinoma; carcinoma in situ of the cervix; stage i endometrial cancer with less than 50% invasion of the myometrium, or other adequately treated stage i or ii cancer in complete remission. * age \> 18 years at the time of consent * written informed consent and hipaa authorization for release of personal health information. * females of childbearing potential must be willing to use an effective method of contraception (hormonal or barrier method of birth control; abstinence) from the time consent is signed until 90 days after treatment discontinuation * females of childbearing potential must have a negative pregnancy test within 7 days prior to being registered for protocol therapy. exclusion criteria: * no known or suspected allergy to sorafenib or any agent given in the course of this trial. * no prior treatment with anti-angiogenesis therapy. * no active cns metastases. * no treatment with any investigational agent within 30 days prior to being registered for protocol therapy. * no concurrent combination anti-retroviral therapy for the treatment of immunodeficiency. * no clinically significant infections requiring antibiotic treatment. * no evidence of bowel obstruction, malabsorption, or other contraindication to oral medication. * no serious non-healing wound, ulcer, or bone fracture. * no major surgery, open biopsy or significant traumatic injury within 28 days of registration for protocol therapy. * no use of st. john's wort or rifampin (rifampicin) while on protocol therapy. * no condition that impairs patient's ability to swallow whole pills.